Atlas of Genetics and Cytogenetics in Oncology and Haematology


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RTN4 (reticulon 4)

Identity

Other namesASY
NI220/250
NOGO
NOGO-A
NSP
NSP-CL
Nbla00271
Nbla10545
RTN-X
RTN4-A
RTN4-B1
RTN4-B2
RTN4-C
HGNC RTN4
Location 2p16.3
Local_order Between FLJ42562 and FLJ31438.
 
  Local order.

DNA/RNA

 
  Genomic structure and transcriptional isoforms.
Description The RTN4 gene spans about 75kb, and contains 9 major exons and several different cap sites (Fig. 2a).
Transcription Three major, RTN4-A, B1 and C, (Fig. 2b) and several minor transcriptional isoforms result from alternative splicing and/or differential promoter usage. Although RTN4 mRNA is ubiquitously expressed, the expression of isoforms is tissue-specific, for example, RTN4-A and C in brain, RTN4-C in muscle, and RTN4-B1 in many other tissues.

Protein

Description Proteins with different sizes are synthesized from different mRNA isoforms: RTN4-A, 129.9 kDa (1192 amino acids); RTN4-B1, 40.3 kDa (373 amino acids); RTN4-B2, 42.3 kDa (392 amino acids); RTN4-C, 22.4 kDa (199 amino acids). All RTN4 protein isoforms retain a common C-terminal domain containing two trans-membrane domains and an endoplasmic reticulum (ER)-retrieval motif.
Expression Ubiquitously expressed (see Transcription).
Localisation RTN4 protein localizes predominantly in the ER and, to a lesser extent, in cytoplasmic membrane.
Function Although definitive functional mechanisms of RTN4 have not yet been clarified, RTN4 protein interacts with several other proteins, including RTN1, RTN3, DP1/Yop1p, BACE1, and Nogo receptor (NogoR). Interaction with DP1/Yop1p, an ER membrane protein, may be necessary for maintenance or stabilization of tubular ER. Binding with BACE1 (beta-amyloid converting enzyme 1) results in reduction in BACE1 activity and production of amyloid-beta. RTN4 also interacts with NogoR, and may lead to activation of RhoA and inhibition of neuronal regeneration in central nervous system. Further, overexpression of RTN4 may cause ER stress and apoptosis in certain cells.
Homology Four reticulon family members (RTN1, RTN2, RTN3 and RTN4) have been identified. They possess a highly conserved C-terminal domain named reticulon homology domain.

Implicated in

Entity Various cancers.
Note Down-regulation of RTN4 expression was observed in small cell lung carcinomas and adult T-cell leukemia/lymphomas, and RTN3, one of RTN4 interacting proteins, was over-expressed in astrocytomas, suggesting involvement of RTN4 (and RTN3) in certain types of tumorigenesis. However, increased incidence of tumor formation has not been observed in RTN4 knock out mice.
RTN4 is also suspected to involve in schizophrenia and neuronal degenerative diseases.
  

External links

Nomenclature
HGNCRTN4   14085
Entrez_GeneRTN4  57142  reticulon 4
Cards
AtlasRTN4ID42182ch2p16
GeneCardsRTN4
EnsemblRTN4 [Search_View]   ENSG00000115310 [Gene_View]
GenatlasRTN4
GeneLynxRTN4
eGenomeRTN4
euGene57142
Genomic and cartography
GoldenPathRTN4  -  2p16.3   chr2:55052831-55090974 -  2p14-p13   [Description]    (hg18-Mar_2006)
EnsemblRTN4 - 2p14-p13 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneRTN4
Gene and transcription
GenbankAB015639 [ ENTREZ ]
GenbankAB020693 [ ENTREZ ]
GenbankAB040462 [ ENTREZ ]
GenbankAB040463 [ ENTREZ ]
GenbankAB073351 [ ENTREZ ]
RefSeqNM_007008 [ SRS ]    NM_007008 [ ENTREZ ]
RefSeqNM_020532 [ SRS ]    NM_020532 [ ENTREZ ]
RefSeqNM_153828 [ SRS ]    NM_153828 [ ENTREZ ]
RefSeqNM_207520 [ SRS ]    NM_207520 [ ENTREZ ]
RefSeqNM_207521 [ SRS ]    NM_207521 [ ENTREZ ]
RefSeqAC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeqAC_000134 [ SRS ]    AC_000134 [ ENTREZ ]
RefSeqNC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeqNT_022184 [ SRS ]    NT_022184 [ ENTREZ ]
RefSeqNW_001838769 [ SRS ]    NW_001838769 [ ENTREZ ]
RefSeqNW_927719 [ SRS ]    NW_927719 [ ENTREZ ]
AceViewRTN4 AceView - NCBI
UnigeneHs.637850 [ SRS ]    Hs.637850 [ NCBI ]     HS637850 [ spliceNest ]
Fast-db18039 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ3LIF1 [ SRS]    Q3LIF1 [ EXPASY ]     Q3LIF1 [ INTERPRO ]     Q3LIF1 [ UNIPROT ]
InterproIPR003388 Reticulon [ SRS ]    IPR003388 Reticulon [ EBI ]
CluSTrQ3LIF1
BlocksQ3LIF1
HPRD07259
Protein Interaction databases
DIPQ3LIF1
IntActQ3LIF1
Polymorphism : SNP, mutations, diseases
OMIM604475    [ map ]   
GENECLINICS604475
SNPRTN4 [dbSNP-NCBI]  
SNPNM_007008 [SNP-NCI]  
SNPNM_020532 [SNP-NCI]  
SNPNM_153828 [SNP-NCI]  
SNPNM_207520 [SNP-NCI]  
SNPNM_207521 [SNP-NCI]  
SNPRTN4 [GeneSNPs - Utah]  RTN4] [HGBASE - SRS]
HAPMAPRTN4 [HAPMAP]  
HGMDRTN4
General knowledge
Family BrowserRTN4 [UCSC Family Browser]
SOURCENM_007008
SOURCENM_020532
SOURCENM_153828
SOURCENM_207520
SOURCENM_207521
SMDHs.637850
SAGEHs.637850
GOprotein binding [Amigo]  protein binding
GOnuclear envelope [Amigo]  nuclear envelope
GOendoplasmic reticulum [Amigo]  endoplasmic reticulum
GOendoplasmic reticulum [Amigo]  endoplasmic reticulum
GOendoplasmic reticulum membrane [Amigo]  endoplasmic reticulum membrane
GOmembrane [Amigo]  membrane
GOintegral to membrane [Amigo]  integral to membrane
GOnegative regulation of anti-apoptosis [Amigo]  negative regulation of anti-apoptosis
GOintegral to endoplasmic reticulum membrane [Amigo]  integral to endoplasmic reticulum membrane
GOregulation of cell migration [Amigo]  regulation of cell migration
GOnegative regulation of axon extension [Amigo]  negative regulation of axon extension
GOregulation of apoptosis [Amigo]  regulation of apoptosis
PubGeneRTN4
TreeFamRTN4
CTD57142 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeRTN4 Related clones (RZPD - Berlin)
PubMed
PubMed63 Pubmed reference(s) in LocusLink

Bibliography

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PMID 10667780
 
A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity.
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Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping.
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PMID 10773680
 
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Axon regeneration in young adult mice lacking Nogo-A/B.
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Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4.
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PMID 12488097
 
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PMID 12811824
 
Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury.
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PMID 12718855
 
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PMID 12718856
 
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PMID 15034570
 
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Nature medicine. 2004 ; 10 (9) : 959-965.
PMID 15286784
 
Overexpression of human reticulon 3 (hRTN3) in astrocytoma.
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Clinical neuropathology. 2004 ; 23 (1) : 1-7.
PMID 14986927
 
Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia.
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Human mutation. 2004 ; 24 (6) : 534-535.
PMID 15532024
 
Nogo-B is a new physiological substrate for MAPKAP-K2.
Rousseau S, Peggie M, Campbell DG, Nebreda AR, Cohen P
The Biochemical journal. 2005 ; 391 (Pt 2) : 433-440.
PMID 16095439
 
Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo.
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Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (4) : 1205-1210.
PMID 15647357
 
Human Nogo-C overexpression induces HEK293 cell apoptosis via a mechanism that involves JNK-c-Jun pathway.
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PMID 16905119
 
ER stress triggers apoptosis induced by Nogo-B/ASY overexpression.
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PMID 16687140
 
Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein.
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The European journal of neuroscience. 2006 ; 24 (5) : 1237-1244.
PMID 16965550
 
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PMID 17022955
 
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PMID 16723274
 
Down-regulation of ASY/Nogo transcription associated with progression of adult T-cell leukemia/lymphoma.
Shimakage M, Inoue N, Ohshima K, Kawahara K, Oka T, Yasui K, Matsumoto K, Inoue H, Watari A, Higashiyama S, Yutsudo M
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PMID 16646068
 
A class of membrane proteins shaping the tubular endoplasmic reticulum.
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PMID 16469703
 
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Reticulon proteins: emerging players in neurodegenerative diseases.
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PMID 16505974
 
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Contributor(s)

Written01-2007Masuo Yutsudo

Citation

This paper should be referenced as such :
Yutsudo M . RTN4 (reticulon 4). Atlas Genet Cytogenet Oncol Haematol. January 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/RTN4ID42182ch2p16.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Aug 11 21:17:19 2008


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